13 February, 2017

25,000 genes

200 immunity genes

6 class I HLA genes

1958 HLA I gene identified

About 12,000 idenitified to date

DNA, RNA and protein

Possibility, potential and actual | Alleles and allotypes

1986 Alain Townsend

What HLA proteins are showing the immune system

1987 Pamela Bjorkman

The structure of the HLA protein

Peptide length distribution

Peptides are catergorical, from 20 amino acid alphabet e.g. LLFGYPVYV

Recap

  • There are thousands of these HLA genes
  • We each have up to 6 HLA genes expressing HLA proteins
  • HLA proteins present peptides
  • 100 x 103 HLA molecules per cell
  • 10 x 103 unique peptides per cell
  • Peptides are coded in a 20 letter amino acid alphabet
  • Peptide length ranges mostly 8-15 amino acids. 9-mers dominate.
  • And that's how T-cells know what is going inside cells

How do chemicals cause allergic responses?

Aim

Characterise the peptidomes of skin cells \(\pm\)DNCB to identify allergenic peptides

Technical and cost limitations

  • 1,000 GBP per replicate
  • 4-6 weeks per replicate
  • Recovery is 1-3% of total peptides.

Replication: Bassani-Sternberg et al. 2015

Replication: Bassani-Sternberg et al. 2015

Quantifying uncertainty

  • What is the likelihood that the peptides seen under our two conditions arise from different underlying populations?

Or to put it another way:

  • What is the probability of seeing peptide X, given condition \(+\)DNCB, versus the probability of seeing peptide X in given condition \(-\)DNCB?